Abstract: The present invention relates to polypeptides that bind to RANK and comprise amino acid sequences of RANKL external surface loops. The invention also relates to fragments, analogs, and derivatives of such polypeptides.

Abstract: The present invention provides non-naturally occurring proteins that bind to RANK and polynucleotides encoding the same. The proteins of the invention can be used for enhancing bone formation by either inhibiting bone resorption or inducing osteogenesis.

Abstract: Method of screening osteogenic compounds utilizing RANK and/or RANK pathway, compositions comprising compounds selected thereby and method for enhancing bone mass comprising administering to a subject an effective amount of said compositions.

Abstract: The present invention provides crystals of RANKL ectodomain complexes, detailed three dimensional structural information illustrating the interaction between RANKL and RANK and methods of utilizing the X-ray crystallographic data from such crystals and other structural data disclosed to design, identify and screen for compounds that modulate activity. The present invention also relates to machine readable media embedded with the three-dimensional atomic structure coordinates of RANKL crystalline complexes and subsets thereof, together with other structural data disclosed herein.

Abstract: A method of enhancing bone formation comprising administering an effective amount of 1) an oligomeric complex of one or more of RANKL, a RANKL fusion protein or an analog, derivative or mimic thereof, 2) an osteogenic compound capable of enhancing activity of one or more intracellular proteins in osteoblasts or osteoblast precursors, wherein said activity is indicative of bone formation, or 3) an osteogenic compound capable of inactivating one or more phosphatases in osteoblasts or osteoblast precursors, wherein said inactivation is indicative of bone formation. The method also may be used to treat a disease or condition manifested at least in part by the loss of bone mass by administering to a patient a pharmaceutical composition comprising an oligomeric complex or osteogenic compound disclosed herein.